Summer Skin Relief PROMOTIO Relief for your patients. Rewards for your practice. The Zoetis Anti-Infective Portfolio Pioneering brands you trust Click Here to Shop ow IJECTABLE CEPHALOSPORI One injection for up to 4 days of continuous antibiotic therapy* Quickly treats common skin infections in dogs and cats First-time resolution and 00% compliance ORAL CEPHALOSPORI When an oral option is preferred, your choice for treatment of common canine skin infections Long half-life results in once-daily dosing for improved compliance Tablets are film coated, odorless and scored for easier administration FLUOROQUIOLOE The fluoroquinolone with the longest half-life for convenient, once-daily dosing Highest known tissue concentrations in the skin, kidney and lung of the dog compared with other veterinary-approved fluoroquinolones at the lowest recommended dose,2 IMPORTAT SAFETY IFORMATIO: People with known hypersensitivity to penicillin or cephalosporins should avoid exposure to and SIMPLICEF. Do not use these products in animals with a history of allergic reactions to penicillins or cephalosporins. Side effects of for both dogs and cats include vomiting, diarrhea, decreased appetite/anorexia and lethargy. Please see full Prescribing Information for and SIMPLICEF. ZEIQUI is not recommended for use in immature cats or dogs during the rapid growth phase, or in cats or dogs known to be hypersensitive to fluoroquinolones. People with a history of hypersensitivity to fluoroquinolones should avoid this product. See full Prescribing Information. *In clinical studies, a single injection of was clinically equivalent to a 4-day antibiotic regimen. In a U.S. efficacy study, only 4% of dogs treated for skin infections required a second injection. ZEIQUI U.S. Prescribing Information ADA #4-5. 203. 2 Scheer M. Concentrations of active ingredient in the serum and in tissues after oral and parenteral administration of Baytril. Vet Med Rev. 987;2:04-8.
Purchase across the portfolio. Earn higher rewards. Summer Skin Relief PROMOTIO Relief for your patients. Rewards for your practice.. Qualify on at least two Zoetis anti-infectives by purchasing a minimum of $500 per product during the promotion period. 2. You will accumulate the following rebate percentage, to be applied to all qualifying purchases within the promotion period: 5% SIMPLICEF ZEIQUI 5% 5% As you buy across the portfolio, the rebate for your total purchase increases. SIMPLICEF 5% + = TOTAL REBATE 5% 0% 3. The rebate percentage accumulated during the offer period will be applied to all qualifying products purchased from Zoetis or an authorized distributor. 4. You will receive your rebate in the form of an account credit. ZEIQUI 5% + = TOTAL REBATE 5% 0% SIMPLICEF 5% SIMPLICEF ZEIQUI 5% + 5% + 5% = + ZEIQUI 5% = TOTAL REBATE 0% TOTAL REBATE 5% Rebates apply to qualifying purchases placed and invoiced from June July 5, 206 Click Here to Shop ow All trademarks are the property of Zoetis Services LLC or a related company or a licensor unless otherwise noted. 206 Zoetis Services LLC. All rights reserved. AIF-00348
(cefovecin sodium) Antimicrobial for Subcutaneous Injection in and Only CAUTIO: Federal (USA) law restricts this drug to use by or on the order of a licensed veterinarian. DESCRIPTIO: Cefovecin sodium is a semi-synthetic broad-spectrum antibacterial agent from the cephalosporin class of chemotherapeutic agents. Cefovecin is the non-proprietary designation for (6R,7R)-7-[[(2Z)-(2-amino-4-thiazolyl)(methoxyimino)acetyl]amino]-8-oxo-3-[(2S)-tetrahydro-2- furanyl]-5-thia--azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid, monosodium salt. Figure : Chemical structure of cefovecin sodium. Each ml of reconstituted lyophile contains cefovecin sodium equivalent to 80 mg cefovecin, methylparaben.8 mg (preservative), propylparaben 0.2 mg (preservative), sodium citrate dihydrate 5.8 mg and citric acid monohydrate 0. mg, sodium hydroxide or hydrochloric acid as required to adjust ph. IDICATIOS: is indicated for the treatment of skin infections (secondary superficial pyoderma, abscesses, and wounds) in dogs caused by susceptible strains of Staphylococcus intermedius and Streptococcus canis (Group G). is indicated for the treatment of skin infections (wounds and abscesses) in cats caused by susceptible strains of Pasteurella multocida. DOSAGE AD ADMIISTRATIO: should be administered as a single subcutaneous injection of 3.6 mg/lb (8 mg/kg) body weight. A second subcutaneous injection of 3.6 mg/lb (8 mg/kg) may be administered if response to therapy is not complete. The decision for a second injection for any individual dog should take into consideration such factors as progress toward clinical resolution, the susceptibility of the causative organisms, and the integrity of the dog s host-defense mechanisms. Therapeutic drug concentrations after the first injection are maintained for 7 days for S. intermedius infections and for 4 days for S. canis (Group G) infections. Maximum treatment should not exceed 2 injections. should be administered as a single, one-time subcutaneous injection at a dose of 3.6 mg/lb (8 mg/kg) body weight. After an injection of, therapeutic concentrations are maintained for approximately 7 days for Pasteurella multocida infections. General Dosing Information A sample of the lesion should be obtained for culture and susceptibility testing prior to beginning antimicrobial therapy. Once results become available, continue with appropriate therapy. If acceptable response to treatment is not observed, or if no improvement is seen within 3 to 4 days, then the diagnosis should be re-evaluated and appropriate alternative therapy considered. may persist in the body for up to 65 days. The effect of remaining concentrations of cefovecin on any subsequent antimicrobial therapies has not been determined. Fluoroquinolone and aminoglycoside antimicrobials have been reported to be compatible with cephalosporin antimicrobial agents.,2,3 Table : Dose Table for at 8 mg/kg Body Weight. Weight of Animal Volume of (3.6 mg/lb or 0.045 ml/lb) 5 lb 0.23 ml 0 lb 0.45 ml 5 lb 0.67 ml 20 lb 0.90 ml 40 lb.80 ml 80 lb 3.60 ml PREPARATIO OF SOLUTIO FOR IJECTIO: To deliver the appropriate dose, aseptically reconstitute with 0 ml sterile water for injection. Shake and allow vial to sit until all material is visually dissolved. The resulting solution contains cefovecin sodium equivalent to 80 mg/ml cefovecin. is light sensitive. The vial should be stored in the original carton and refrigerated when not in use. Use the entire contents of the vial within 56 days of reconstitution. COTRAIDICATIOS: is contraindicated in dogs and cats with known allergy to cefovecin or to β-lactam (penicillins and cephalosporins) group antimicrobials. Anaphylaxis has been reported with the use of this product in foreign market experience. If an allergic reaction or anaphylaxis occurs, should not be administered again and appropriate therapy should be instituted. Anaphylaxis may require treatment with epinephrine and other emergency measures, including oxygen, intravenous fluids, intravenous antihistamine, corticosteroids, and airway management, as clinically indicated. Adverse reactions may require prolonged treatment due to the prolonged systemic drug clearance (65 days). WARIGS: ot for use in humans. Keep this and all drugs out of reach of children. Consult a physician in case of accidental human exposure. For subcutaneous use in dogs and cats only. Antimicrobial drugs, including penicillins and cephalosporins, can cause allergic reactions in sensitized individuals. To minimize the possibility of allergic reactions, those handling such antimicrobials, including cefovecin, are advised to avoid direct contact of the product with the skin and mucous membranes. PRECAUTIOS: Prescribing antibacterial drugs in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit to treated animals and may increase the risk of the development of drug-resistant animal pathogens. The safe use of in dogs or cats less than 4 months of age (see Animal Safety) and in breeding or lactating animals has not been determined. Safety has not been established for IM or IV administration. The long-term effects on injection sites have not been determined. is slowly eliminated from the body, approximately 65 days is needed to eliminate 97% of the administered dose from the body. Animals experiencing an adverse reaction may need to be monitored for this duration. has been shown in an experimental in vitro system to result in an increase in free concentrations of carprofen, furosemide, doxycycline, and ketoconazole. Concurrent use of these or other drugs that have a high degree of protein-binding (e.g. SAIDs, propofol, cardiac, anticonvulsant, and behavioral medications) may compete with cefovecin-binding and cause adverse reactions. Positive direct Coombs test results and false positive reactions for glucose in the urine have been reported during treatment with some cephalosporin antimicrobials. Cephalosporin antimicrobials may also cause falsely elevated urine protein determinations. Some antimicrobials, including cephalosporins, can cause lowered albumin values due to interference with certain testing methods. Occasionally, cephalosporins and SAIDs have been associated with myelotoxicity, thereby creating a toxic neutropenia 4. Other hematological reactions seen with cephalosporins include neutropenia, anemia, hypoprothrombinemia, thrombocytopenia, prolonged prothrombin time (PT) and partial thromboplastin time (PTT), platelet dysfunction and transient increases in serum aminotransferases. ADVERSE REACTIOS: A total of 320 dogs, ranging in age from 8 weeks to 9 years, were included in a field study safety analysis. Adverse reactions reported in dogs treated with and the active control are summarized in Table 2. Table 2: umber of * with Adverse Reactions Reported During the Field Study with. Adverse Reaction (n=57) (n=63) Lethargy 2 7 Anorexia/Decreased Appetite 5 8 Vomiting 6 2 Diarrhea 6 7 Blood in Feces 2 Dehydration 0 Flatulence 0 Increased Borborygmi 0 *Some dogs may have experienced more than one adverse reaction or more than one occurrence of the same adverse reaction during the study. Mild to moderate elevations in serum -glutamyl transferase or serum alanine aminotransferase were noted post-treatment in several of the -treated dogs. o clinical abnormalities were noted with these findings. One -treated dog in a separate field study experienced diarrhea post-treatment lasting 4 weeks. The diarrhea resolved. A total of 29 cats, ranging in age from 2.4 months ( cat) to 2 years, were included in the field study safety analysis. Adverse reactions reported in cats treated with and the active control are summarized in Table 3. Table 3: umber of * with Adverse Reactions Reported During the Field Study with. Adverse Reaction (n=47) (n=44) Vomiting 0 4 Diarrhea 7 26 Anorexia/Decreased Appetite 6 6 Lethargy 6 6 Hyper/Acting Strange Inappropriate Urination 0 *Some cats may have experienced more than one adverse reaction or more than one occurrence of the same adverse reaction during the study. Four cases had mildly elevated post-study ALT ( case was elevated pre-study). o clinical abnormalities were noted with these findings. Twenty-four cases had normal pre-study BU values and elevated post-study BU values (37 39 mg/dl post-study). There were 6 cases with normal pre- and mildly to moderately elevated post-study creatinine values. Two of these cases also had an elevated post-study BU. o clinical abnormalities were noted with these findings. One -treated cat in a separate field study experienced diarrhea post-treatment lasting 42 days. The diarrhea resolved. FOREIG MARKET EXPERIECE: The following adverse events were reported voluntarily during post-approval use of the product in dogs and cats in foreign markets: death, tremors/ ataxia, seizures, anaphylaxis, acute pulmonary edema, facial edema, injection site reactions (alopecia, scabs, necrosis, and erythema), hemolytic anemia, salivation, pruritus, lethargy, vomiting, diarrhea, and inappetance. For a copy of the Material Safety Data Sheet (MSDS) or to report a suspected adverse reaction call Zoetis Inc. at -888-963-847. CLIICAL PHARMACOLOGY: Pharmacokinetics Cefovecin is rapidly and completely absorbed following subcutaneous administration. on-linear kinetics is exhibited (plasma concentrations do not increase proportionally with dose). Cefovecin does not undergo hepatic metabolism and the majority of a dose is excreted unchanged in the urine. Elimination also occurs from excretion of unchanged drug in the bile. Cefovecin is a highly protein-bound molecule in dog plasma (98.5%) and cat plasma (99.8%) and may compete with other highly protein-bound drugs for plasma protein-binding sites that could result in transient, higher free drug concentrations of either compound. Pharmacokinetic parameters following subcutaneous dosing at 8 mg/kg in the dog and cat are summarized in Table 4. Table 4: Pharmacokinetic Parameters Reflecting Total Drug Concentrations in Plasma (mean ± standard deviation or range) Following an 8 mg/kg Intravenous or Subcutaneous Dose of Cefovecin in and. PARAMETER MEA ± SD or (Range) p Terminal plasma elimination half-life, T /2 (h)* h 33 ± 6 66 ± 8 AUC 0-inf (μg h/ml)* g 0400 ± 900 p 22700 ± 3450 Time of maximum concentration, T max (h)* h 6.2 (0.5-2.0) 2.0 (0.5-6.0) Maximum concentration, C max ()* a 2 ± 5 4 ± 2 Vd ss (L/kg)** g 0.22 ± 0.0 0.090 ± 0.00 CL total (ml/h/kg)** g 0.76 ± 0.3 p 0.350 ± 0.40 SD = standard deviation p = a phase effect was observed, only data for the first phase are provided (n=6); all other data provided are derived from 2 animals * = SC ** = IV a = arithmetic mean h = harmonic mean g = geometric mean Population Pharmacokinetics Cefovecin plasma concentrations in the dog have been characterized by the use of population pharmacokinetic (PPK) data. Plasma cefovecin concentration data were pooled from 7 laboratory pharmacokinetic studies, each involving young, normal healthy Beagle dogs. The final dataset contained 59 concentration records from 39 dogs. The simulations from the model provide the mean population estimate and the 5 th and 95 th percentile of the population estimates of total and free cefovecin concentrations over time. Figure 2 shows the predicted free plasma concentrations following administration of 8 mg/kg body weight to dogs. Based upon these predicted concentrations, 95% of the canine population will have active (free) drug concentrations > the of S. canis (0.06 ) for approximately 4 days and free concentrations > the for S. intermedius (0.25 ) for approximately 7 days following a single 8 mg/kg subcutaneous injection of cefovecin. (See MICROBIOLOGY). Figure 2: Population Predicted Free Concentration of Cefovecin in Plasma Following a Single Subcutaneous Injection of 8 mg/kg Body Weight in (solid line is population prediction, dotted lines are the 5 th and 95 th percentiles for the population prediction). Cefovecin plasma concentrations in the cat have been characterized by the use of PPK data. Plasma cefovecin concentration data were pooled from 4 laboratory pharmacokinetic studies. The final dataset contained 338 concentration records from 22 cats. The simulations from the model provide the mean population estimate as well as the 5 th and 95 th percentile of the population estimates of total and free cefovecin concentrations over time. Figure 3 displays the predicted free plasma concentrations following administration of 8 mg/kg body weight to cats. Based upon these predicted concentrations, 95% of the feline population will have active (free) drug concentrations > the of Pasteurella multocida (0.06 ) for approximately 7 days when administered a single 8 mg/kg subcutaneous injection of cefovecin. (See MICROBIOLOGY). Figure 3: Population Predicted Free Concentration of Cefovecin in Plasma Following a Single Subcutaneous Injection of 8 mg/kg Body Weight in (solid line is population prediction, dotted lines are the 5 th and 95 th percentiles for the population prediction). MICROBIOLOGY: is a cephalosporin antibiotic. Like other β-lactam antimicrobials, exerts its inhibitory effect by interfering with bacterial cell wall synthesis. This interference is primarily due to its covalent binding to the penicillin-binding proteins (PBPs) (ie, transpeptidase and carboxypeptidase), which are essential for synthesis of the bacterial cell wall. For E. coli, the in vitro activity of is comparable to other cephalosporins, but due to the high-affinity proteinbinding, the in vivo free concentration of cefovecin does not reach the for E. coli (.0 ). is not active against Pseudomonas spp. or enterococci. The minimum inhibitory concentration (MIC) values for cefovecin against label-claim pathogens isolated from skin infections in dogs enrolled in a 200-2003 field effectiveness study are presented in Table 5. All MICs were determined in accordance with the Clinical and Laboratory Standards Institute (CLSI) standards. Table 5: Activity of against Pathogens Isolated from Treated with in Field Studies in the US During 200-2003. Disease Pathogen Microbiological Treatment Outcome umber Sample of Collection Isolates (Time Relative to Treatment) MIC 50 MIC Range Staphylococcus Success 44 Pre-Treatment 0.2 0.25 0.06-2 intermedius Skin Infections Failure 4 Pre-Treatment 0.2-2 Streptococcus Success 6 Pre-Treatment 0.06 0.06 0.06 canis (Group G) Failure 2 Pre-Treatment 0.06 The MIC values for cefovecin against Pasteurella multocida isolated from skin infections (wounds and abscesses) in cats enrolled in a 200-2003 field effectiveness study are presented in Table 6. All MICs were determined in accordance with the CLSI standards. Table 6: Activity of against Pathogens Isolated from Treated with in Field Studies in the US During 200-2003. Disease Pathogen Skin Infections Pasteurella multocida Microbiological Treatment Outcome umber Sample of Collection Isolates (Time Relative to Treatment) MIC 50 MIC Range Success 57 Pre-Treatment 0.06 0.06 0.06-0.2 Failure Pre-Treatment 0.06 EFFECTIVEESS: In a double-masked, : randomized canine field study conducted in the United States, the effectiveness of was compared to a cephalosporin active control. In this study, 320 dogs with superficial secondary pyoderma, abscesses, or infected wounds were treated with either a single injection of (n=57) at 3.6 mg/lb (8 mg/kg) body weight or with an oral active control antibiotic (n=63), administered twice daily for 4 days. In this study, dogs could receive a second course of therapy 4 days after the initial treatment. Of the 320 enrolled dogs, 22 of 57 dogs received 2 treatments of and 35 of 63 dogs received 2 courses of treatment with the active control. In the study, 8 of the 57 enrolled cases were evaluable for effectiveness for, and 7 of the 63 enrolled cases were evaluable for effectiveness of the active control antibiotic. was non-inferior to the active control. Table 7 summarizes the clinical success rates obtained 28 days after the initiation of the final course of therapy. Table 7: Clinical Success Rates by Treatment Group 28 Days after the Initiation of the Final Course of Therapy. Type of Infection Skin (secondary superficial pyoderma, abscesses, and infected wounds) (n=8) (n=7) 09 (92.4%) 08 (92.3%) was administered concomitantly with other commonly used veterinary products such as heartworm preventatives, flea control products, sedatives/tranquilizers, anesthetic agents, routine immunizations, antihistamines, thyroid hormone supplementation, and nonsteroidal anti-inflammatory drugs during the field study. In a double-masked, : randomized cat field study conducted in the United States, the effectiveness of was compared to an active control. In this study, 29 cats with infected wounds or abscesses were treated with either a single injection of (n=47) at 3.6 mg/lb (8 mg/kg) body weight or with an oral active control antibiotic (n=44), administered once daily for 4 days. was non-inferior to the active control. The clinical success rates were obtained 28 days after the initiation of therapy and are presented in Table 8. Table 8: Clinical Success Rates by Treatment Group 28 Days after the Initiation of Therapy. Type of Infection (n=89) (n=88) Skin (wounds and abscesses) 86 (96.6%) 80 (90.9%) was used concomitantly with other commonly used veterinary products such as heartworm preventatives, flea control products, sedatives/tranquilizers, anesthetic agents, and vaccines during the field study. AIMAL SAFETY: administered to healthy 4-month-old dogs at doses of 2 mg/kg (.5X), 36 mg/kg (4.5X), and 60 mg/kg (7.5X) every 7 days by dorsoscapular subcutaneous injections was well-tolerated for a total of 5 doses. Vomiting and diarrhea were seen in all treatment groups, with the incidence of vomiting and the incidence and duration of diarrhea increasing in a dose-related manner. Injection site irritation and transient edema occurred with increasing frequency in a dose-related manner and with repeat injections. Two injection site reactions included a seroma over the shoulder and swelling lasting > 30 days. dosed at 36 mg/kg had a significant (P=0.0088) increase in BU (all means remained within the normal range) compared to the controls. One dog dosed at 60 mg/kg exhibited a glomerulopathy on histopathology, and dog in this same group had minimal peliosis hepatis. At an exaggerated dose of 80 mg/kg (22.5X) in dogs, caused some injection site irritation, vocalization, and edema. Edema resolved within 8-24 hours. administered to healthy 4-month-old cats at doses of 2 mg/kg (.5X), 36 mg/kg (4.5X), and 60 mg/kg (7.5X) every 7 days by dorsoscapular subcutaneous injections was well-tolerated for a total of 5 doses. Vomiting and diarrhea were observed in cats, with the incidence of vomiting and the incidence and duration of diarrhea increasing in a dose-related manner. The mean albumin values for all the -treated cats were significantly lower (P 0.05) than the control values (all means remained within the normal range) for all time periods. The mean alkaline phosphatase values in the 60 mg/kg group were significantly higher (P 0.029) than the control values for all time periods. Injection-site irritation and transient edema occurred with increasing frequency in a doserelated manner and with repeat injections. One cat in the 2 mg/kg group had a mild renal tubular and interstitial fibrosis, and cat in the 2 mg/kg group had mild glomerulosclerosis on histopathology. At an exaggerated dose of 80 mg/kg (22.5X), was associated with injection site irritation, vocalization, and edema. Edema resolved within 8-24 hours. On day 0, cats had lower mean white blood cell counts compared to the controls. One cat had a small amount of bilirubinuria on day 0. STORAGE IFORMATIO: Store the powder and the reconstituted product in the original carton, refrigerated at 2 to 8 C (36 to 46 F). Use the entire contents of the vial within 56 days of reconstitution. PROTECT FROM LIGHT. After each use it is important to return the unused portion back to the refrigerator in the original carton. As with other cephalosporins, the color of the solution may vary from clear to amber at reconstitution and may darken over time. If stored as recommended, solution color does not adversely affect potency. HOW SUPPLIED: is available as a 0 ml multi-use vial containing 800 milligrams of cefovecin as a lyophilized cake. REFERECES: Pillai SK, Moellering RC, Eliopoulos GM. Antimicrobial combinations. In: Lorian V, ed. Antibiotics in laboratory medicine. 5th ed. Philadelphia, PA: Lippincott Williams & Wilkins, 2005;365-440. 2 Fish D, Choi MK, Jung R. Synergic activity of cephalosporins plus fluoroquinolones against Pseudomonas aeruginosa with resistance to one or both drugs. J Antimicrob Chemother 2002;50:045-049. 3 Mayer I, agy E. Investigation of the synergic effects of aminoglycoside-fluoroquinolone and third-generation cephalosporin combinations against clinical isolates of Pseudomonas spp. J Antimicrob Chemother 999;43:65-657. 4 Birchard SJ, Sherding RG. Saunders manual of small animal practice. 2nd ed. Philadelphia: PA: WB Saunders Co, 2000;66. ADA# 4-285, Approved by FDA Distributed by Zoetis Inc. January 203 Kalamazoo, MI 49007 PAA035845A&P
For Oral Use In Only CAUTIO: Federal (USA) law restricts this drug to use by or on the order of a licensed veterinarian. DESCRIPTIO Cefpodoxime proxetil is an orally administered, extended spectrum, semi-synthetic cephalosporin antibiotic. The chemical name is: (+/-)--Hydroxyethyl(+)-(6R,7R)-7-[2-(2-amino-4-thiazolyl) glyoxylamido]-3-methoxymethyl)-8-oxo-5-thia--azabicyclo[4.2.0] oct-2-ene-2-carboxylate, 7 2 -(Z)-(O-methyloxime), isopropyl carbonate (ester) [87239-8-4]. Cefpodoxime proxetil Chemical Structure: Cefpodoxime proxetil is a prodrug; its active metabolite is cefpodoxime. All doses of SIMPLICEF (cefpodoxime proxetil) tablets are expressed in terms of the active cefpodoxime moiety. SIMPLICEF is available as: 00 mg Tablet, each reddish-orange, elliptical, scored tablet contains cefpodoxime proxetil equivalent to 00 mg of cefpodoxime. 200 mg Tablet, each light orange, round rectangle, scored tablet contains cefpodoxime proxetil equivalent to 200 mg of cefpodoxime. IDICATIO SIMPLICEF tablets are indicated for the treatment of skin infections (wounds and abscesses) in dogs caused by susceptible strains of Staphylococcus intermedius, Staphylococcus aureus, Streptococcus canis (group G, ß hemolytic), Escherichia coli, Pasteurella multocida, and Proteus mirabilis. DOSAGE AD ADMIISTRATIO Dose range: The dose range of SIMPLICEF (cefpodoxime proxetil) tablets is 5-0 mg/kg (2.3-4.5 mg/lb) body weight, administered orally, once a day. The dose may be given with or without food. The determination of dosage for any particular patient must take into consideration such factors as the severity and nature of the infection, the susceptibility of the causative organisms, and the integrity of the patient s host-defense mechanisms. Obtain a sample of the pathogenic organism for culture and sensitivity testing prior to beginning antimicro bial therapy. Once results become available, continue with appropriate therapy. Duration: SIMPLICEF tablets should be administered once daily for 5-7 days or for 2-3 days beyond the cessa tion of clinical signs, up to a maximum of 28 days. Treatment of acute infections should not be continued for more than 3-4 days if no response to therapy is seen. Dosing Charts: For daily oral administration of SIMPLICEF at 5 mg/kg (Table ) and 0 mg/kg (Table 2). Table. Dose Table for SIMPLICEF Tablets at 5 mg/kg Total Daily Dosage Weight of Dog (lbs) Daily Dose 22 44 66 88 32 o. of 00 mg tablets 0.5.5 o. of 200 mg tablets Weight of Dog (kgs) Daily Dose 0 20 30 40 60 o. of 00 mg tablets 0.5.5 o. of 200 mg tablets Table 2. Dose Table for SIMPLICEF Tablets at 0 mg/kg Total Daily Dosage Weight of Dog (lbs) Daily Dose 22 44 66 88 32 o. of 00 mg tablets 0.5 o. of 200 mg tablets 2 3 Weight of Dog (kgs) Daily Dose 5 0 20 30 40 60 o. of 00 mg tablets 0.5 o. of 200 mg tablets 2 3 COTRAIDICATIOS Cefpodoxime proxetil is contraindicated in dogs with known allergy to cefpodoxime or to the ß-lactam (penicillins and cephalosporins) group of antibiotics. WARIGS ot for human use. Keep this and all drugs out of reach of children. Antimicrobial drugs, including penicillins and cephalosporins, can cause allergic reactions in sensitized individuals. To minimize the possibility of allergic reactions, those handling such antimicrobials, including cefpodoxime, are advised to avoid direct contact of the product with the skin and mucous membranes. PRECAUTIOS The safety of cefpodoxime proxetil in dogs used for breeding, pregnant dogs, or lactating bitches has not been demonstrated. As with other cephalosporins, cefpodoxime proxetil may occasionally induce a positive direct Coombs test. ADVERSE REACTIOS A total of 26 dogs of various breeds and ages ranging from 2 months to 5 years were included in the field study safety analysis. The following table shows the number of dogs displaying each clinical observation. Table 3. Abnormal Health Findings in the U.S. Field Study Clinical Observation SIMPLICEF (n=8) Active Control (n=98) Vomiting 2 4 Diarrhea Increased water 0 2 drinking Decreased appetite may have experienced more than one of the observations during the study. To report a suspected adverse reaction call -888-963-847. To request a material safety data sheet (MSDS) for SIMPLICEF tablets, call -888-963-847. CLIICAL PHARMACOLOGY Pharmacokinetics/Pharmacodynamics: Cefpodoxime proxetil is a prodrug that is absorbed from and de-esterified in the gastrointestinal tract to its active metabolite, cefpodoxime. Following oral administration to fasting Beagles, oral bioavailability was 63. ± 5.3%. Figure. Canine Plasma Concentration of Cefpodoxime After a Single Oral Dose of 0 mg/kg Cefpodoxime Proxetil Tablets Cefpodoxime is distributed in the body with an apparent volume of distribution of 5 ± 27 ml/kg. Like other ß-lactam antibiotics, cefpodoxime is eliminated from the body primarily in the urine, with an apparent elimination half-life of approximately 5-6 hours after oral administration. This is similar to the 4.7 hour apparent elimination half-life observed after intravenous dosing. Following intravenous administration of 0 mg/kg, the average total body clearance (Cl B ) was 22.7 ± 4.9 ml/hr/kg. Table 4. Summary of Pharmacokinetic Parameters Obtained after a Single Oral Dose of 0 mg Cefpodoxime/kg BW, Administered as a Tablet PK Parameter Unit Tablet (SD) AUC 0- mcg hr/ml 45 (77.6) AUC 0-LOQ mcg hr/ml 42 (77.5) Maximum concentration (C max ) Terminal plasma elimination half-life (t /2,z ) Time of maximum concentration (t max ) mcg/ml 6.4 (.8) hr 5.6 (.5) hr 2.2 (0.542) Mean residence time hr 9.2 (.97) (MRT 0- ) Microbiology: Like other ß-lactam antibiotics, cefpodoxime exerts its inhibitory effect by interfering with bacterial cell wall synthesis. This interference is primarily due to its covalently binding to the penicillin-binding proteins (PBPs) (i.e. transpeptidase and/or carboxypeptidase), which are essential for synthesis of the bacterial cell wall. Therefore, cefpodoxime is bactericidal. Cefpodoxime is stable in the presence of many common ß-lactamase enzymes. As a result, many organisms resistant to other ß-lactam antibiotics (penicillins and some cephalosporins) due to the production of ß-lactamases may be susceptible to cefpodoxime. Cefpodoxime has a broad spectrum of clinically useful antibacterial activity that includes staphylococci, streptococci, and Gram-negative species (including Pasteurella, Escherichia, and Proteus). The compound is not active against most obligate anaerobes, Pseudomonas spp., or enterococci. The minimum inhibitory concentrations (MICs) for cefpodoxime against Grampositive and Gram-negative pathogens isolated from canine skin infections (wounds and abscesses) in a 2002 U.S. field study are presented in Table 5. All MICs were determined in accordance with the ational Committee for Clinical Laboratory Standards (CCLS). Appropriate quality control (QC) ranges for in vitro susceptibility testing are presented in Table 6. Table 5. Cefpodoxime Minimum Inhibitory Concentration Values (mcg/ml) from a 2002 Field Study Evaluating Skin Infections (wounds and abscesses) of Canines in the United States. Organism* # of Isolates MIC 50 Range Staphylococcus 8 0.2 0.50 0.2->32.0 intermedius Streptococcus 33 0.03 0.03 0.03 canis (group G, ß hemolytic) Escherichia coli 4 0.25 0.50 0.2->32.0 Pasteurella 32 0.03 0.03 0.03-0.2 multocida Proteus mirabilis 4 0.03 0.06 0.03-0.06 Staphylococcus aureus 9 2.0 2.0 0.2-2.0 o Range, all isolates yielded the same value. * Veterinary specific interpretive criteria have not been established for the above listed canine pathogens by the CCLS at this time. Table 6. Acceptable Quality Control Ranges for Cefpodoxime QC ATCC strain Escherichia coli 25922 Staphylococcus aureus 25923 Staphylococcus aureus 2923 Streptococcus pneumoniae 4969 KB Disk Diffusion Method Drug concentration Zone diameter Broth Micro-dilution Method MIC 0 mcg 23-28 mm a 0.25- mcg/ml a 0 mcg 9-25 mm a -8 mcg/ml a 0 mcg 28-34 mm b 0.03-0.2 mcg/ml b a These ranges are for quality control strains used to monitor accuracy of minimum inhibitory concentrations (MICs) of nonfastidious organisms using cation-adjusted Mueller-Hinton agar or broth medium. The dilution range should encompass the QC ranges of these strains in the broth micro-dilution method. b These ranges are for quality control strains used to monitor accuracy of minimum inhibitory concentrations (MICs) of fastidious organisms. When susceptibility testing is performed for Streptococcus canis (group G, ß hemolytic), Strep to coccus pneumoniae ATCC 4969 should be included as a QC strain in the presence of 5% lysed sheep blood (KB disk diffusion method) or 2.5% lysed horse blood (broth micro- dilution method). EFFECTIVEESS The clinical effectiveness of SIMPLICEF (cefpodoxime proxetil) was established in a multi-location (23 site) field study. In this study, 26 dogs with infected wounds or abscesses were treated with either SIMPLICEF (n=8) once daily at 5 mg/ kg (2.3 mg/lb) body weight or with a active control antibiotic (n=98) administered twice daily for 5-7 days. In this study, SIMPLICEF was considered noninferior to the active control (88.7% versus 88.4% respectfully) in the treatment of canine skin infections (wounds and abscesses) caused by susceptible strains of Staphylococcus intermedius, Staphylococcus aureus, Streptococcus canis (group G, ß hemolytic), Escherichia coli, Pasteurella multocida, and Proteus mirabilis. AIMAL SAFETY In target animal safety studies, cefpodoxime was well tolerated at exaggerated daily oral doses of 00 mg/kg/day (0 times the maximum label dose) for 3 weeks in adult dogs and for 28 days in puppies (8-23 days of age). Therefore, once daily administration of cefpodoxime oral tablets at the maximum labeled dose of 0 mg/kg for up to 28 days was shown to be safe in adult dogs and puppies. Blood dyscrasia including neutropenias, may be seen following high doses of cephalosporins. Cephalosporin administration should be discontinued in such cases. STORAGE IFORMATIO Store tablets at controlled room temperature 20 to 25 C (68 to 77 F). Replace cap securely after each opening. HOW SUPPLIED SIMPLICEF tablets are available in the following strengths (cefpodoxime equivalent), colors, and sizes: 00 mg (reddish-orange, elliptical, scored, debossed with 5228) Bottles of 00 Bottles of 250 200 mg (light orange, round rectangle, scored, debossed with 5229) Bottles of 00 Bottles of 250 ADA # 4-232, Approved by FDA Manufactured by: Sandoz Kundl, Austria Product of India Distributed by: Zoetis Inc. Kalamazoo, MI 49007 Revised June 203 4604787A&P
Figure 2: Mean plasma concentrations (µg/ml) following single oral administration of marbofloxacin to adult beagle dogs at dosages of.25 mg/lb or 2.5 mg/lb. * See Table 4 in Microbiology section for MIC data. Tablets For oral use in dogs and cats only CAUTIO: Federal law restricts this drug to use by or on the order of a licensed veterinarian. Federal law prohibits the extralabel use of this drug in food-producing animals. DESCRIPTIO: Marbofloxacin is a synthetic broad-spectrum antibacterial agent from the fluoroquinolone class of chemotherapeutic agents. Marbofloxacin is the non-proprietary designation for 9-fluoro-2,3-dihydro-3-methyl-0-(4-methyl-- piperazinyl)-7-oxo-7h-pyrido[3,2,-ij][4,,2] benzoxadiazine-6-carboxylic acid. The empirical formula is C 7 H 9 F 4 O 4 and the molecular weight is 362.36. The compound is soluble in water; however, solubility decreases in alkaline conditions. The -octanol/water partition coefficient (Kow) is 0.835 measured at ph 7 and 25 C. Figure : Chemical structure of marbofloxacin F O O OH Figure 3: Mean plasma concentrations (µg/ml) following single oral administration of marbofloxacin to adult cats at a dosage of 2.5 mg/lb. * See Table 5 in Microbiology section for MIC data. H 3 C O CH 3 CLIICAL PHARMACOLOGY: Marbofloxacin is rapidly and almost completely absorbed from the gastrointestinal tract following oral administration to fasted animals. Divalent cations are generally known to diminish the absorption of fluoroquinolones. The effects of concomitant feeding on the absorption of marbo floxacin have not been determined. (See Drug Interactions.) In the dog, approximately 40% of an oral dose of marbofloxacin is excreted unchanged in the urine. Excretion in the feces, also as unchanged drug, is the other major route of elimination in dogs. Ten to 5% of marbofloxacin is metabolized by the liver in dogs. In vitro plasma protein binding of marbofloxacin in dogs was 9.% and in cats was 7.3%. In the cat, approximately 70% of an oral dose is excreted in the urine as marbofloxacin and metabolites with approximately 85% of the excreted material as unchanged drug. Pharmacokinetic parameters related to intravenous dosing were estimated in a study of 6 healthy adult beagle dogs, and are summarized in Table. The absolute bioavailability following dosing of oral tablets to the same animals was 94%. Marbofloxacin plasma concentrations were determined over time in healthy adult beagle dogs (6 dogs per dosage group) following single oral doses of.25 mg/lb or 2.5 mg/lb. Absorption of orally administered marbofloxacin increases proportionally over the dose range of.25 to 2.5 mg/lb. Marbofloxacin plasma concentrations were determined over time in 7 healthy adult male cats following a single oral dose of 2.5 mg/lb. Plasma pharmacokinetic parameters following oral dosing of dogs and cats are summarized in Figures 2 and 3 and in Table 2. Based on the terminal elimination half-life and the dosing interval, steady-state levels are reached after the third dose and are expected to be approximately 25% greater in dogs and 35% greater in cats than those achieved after a single dose. Marbo floxacin is widely distributed in canine tissues. Tissue concentrations of marbo floxacin were determined in healthy male beagle dogs (4 dogs per time period) at 2, 8 and 24 hours after a single oral dose (.25 or 2.5 mg/lb) and are summarized in Tables 3a and 3b. Table : Mean pharmacokinetic parameters following intravenous administration of marbofloxacin to 6 adult beagle dogs at a dosage of 2.5 mg/lb. Estimate ± SD* Parameter n=6 Total body clearance, (ml/h kg) 94 ± 8 Volume of distribution at steady state, V ss, (L/kg).9 ± 0.08 AUC 0-inf (µg h/ml) 59 ± 5 Terminal plasma elimination half-life, t /2 (h) 9.5 ± 0.7 Table 2: Mean pharmacokinetic parameters following oral administration of marbofloxacin tablets to adult beagle dogs at a nominal dosage of.25 mg/lb or 2.5 mg/lb and to cats at 2.5 mg/lb. Dog Dog Cat Estimate ± SD* Estimate ± SD* Estimate ± SD* Parameter (.25 mg/lb) (2.5 mg/lb) (2.5 mg/lb) n=6 n=6 n=7 Time of maximum concentration, T max (h).5 ± 0.3.8 ± 0.3.2 ± 0.6 Maximum concentration, C max, (µg/ml) 2.0 ± 0.2 4.2 ± 0.5 4.8 ± 0.7 AUC 0-inf (µg h/ml) 3.2 ±.6 64 ± 8 70 ± 6 Terminal plasma elimination half-life, t /2 (h) 0.7 ±.6 0.9 ± 0.6 2.7 ±. mean actual dosages administered to dogs were.22 mg/lb and 2.56 mg/lb, respectively, and the mean actual dosage administered to cats was 2.82 mg/lb. Table 3a: Tissue distribution following a single oral administration of marbofloxacin tablets to adult beagle dogs at a dosage of.25 mg/lb*. Marbofloxacin Concentrations (µg/g ± SD) 2 hours 8 hours 24 hours Tissue (n=4) (n=4) (n=4) bladder 4.8 ±. 2.6 ±.5. ± 0.9 bone marrow 3. ± 0.5.5 ±.5 0.7 ± 0.2 feces 5 ± 9 48 ± 40 26 ± jejunum 3.6 ± 0.5.3 ±.0 0.7 ± 0.3 kidney 7. ±.7.4 ± 0.5 0.9 ± 0.3 lung 3.0 ± 0.5 0.8 ± 0.2 0.57 ± 0.9 lymph node 5.5 ±..3 ± 0.3.0 ± 0.3 muscle 4. ± 0.3.0 ± 0.3 0.7 ± 0.2 prostate 5.6 ±.4.8 ± 0.6. ± 0.4 skin.9 ± 0.6 0.4 ± 0.3 0.32 ± 0.08 Table 3b: Tissue distribution following a single oral administration of marbofloxacin tablets to adult beagle dogs at a dosage of 2.5 mg/lb. Marbofloxacin Concentrations (µg/g ± SD*) 2 hours 8 hours 24 hours Tissue (n=4) (n=4) (n=4) bladder 2 ± 4 6 ± 7.8 ± 0.4 bone marrow 4.6 ±.5.28 ± 0.3 0.9 ± 0.3 feces 8 ± 3 52 ± 7 47 ± 28 jejunum 7.8 ±. 2.0 ± 0.3. ± 0.3 kidney 2.7 ±.7 2.7 ± 0.3.6 ± 0.2 lung 5.48 ± 0.7.45 ± 0.9.0 ± 0.2 lymph node 8.3 ± 0.7 2.3 ± 0.5 2.03 ± 0.06 muscle 7.5 ± 0.5.8 ± 0.3.20 ± 0.2 prostate ± 3 2.7 ±.0 2.0 ± 0.5 skin 3.20 ± 0.33 0.705 ± 0.03 0.46 ± 0.09 Microbiology: The primary action of fluoroquinolones is to inhibit the bacterial enzyme, DA gyrase. In susceptible organisms, fluoroquinolones are rapidly bactericidal at relatively low concentrations. Marbofloxacin is bactericidal against a broad range of gram-negative and gram-positive organisms. The minimum inhib itory concentrations (MICs) of pathogens isolated in clinical field studies performed in the United States were determined using ational Committee for Clinical Labo ra tory Standards (CCLS) standards, and are shown in Tables 4 and 5. 390600 A&P
Table 4: MIC Values* (µg/ml) of marbofloxacin against pathogens isolated from skin, soft tissue and urinary tract infections in dogs enrolled in clinical studies conducted during 994 996. o. of Organism Isolates MIC 50 MIC Range Staphylococcus intermedius 35 0.25 0.25 0.25 2 Escherichia coli 6 0.03 0.06 0.05 2 Proteus mirabilis 35 0.06 0.25 0.03 0.25 Beta-hemolytic Streptococcus, (not Group A or Group B) 25 2 0.5 6 Streptococcus, Group D enterococcus 6 4 0.008 4 Pasteurella multocida 3 0.05 0.06 0.008 0.5 Staphylococcus aureus 2 0.25 0.25 0.25 0.5 Enterococcus faecalis 2 2 4 Klebsiella pneumoniae 0.06 0.06 0.0 0.06 Pseudomonas spp. 9 ** ** 0.06 Pseudomonas aeruginosa 7 ** ** 0.25 * The correlation between in vitro susceptibility data (MIC) and clinical response has not been determined. ** MIC 50 and not calculated due to insufficient number of isolates. Table 5: MIC Values* (µg/ml) of marbofloxacin against pathogens isolated from skin and soft tissue infections in cats enrolled in clinical studies conducted in 995 and 998. o. of Organism Isolates MIC 50 MIC Range Pasteurella multocida 35 0.03 0.06 0.008 0.25 Beta-hemolytic Streptococcus 22 0.06 Staphylococcus aureus 2 0.25 0.5 0.25 Corynebacterium spp. 4 0.5 0.25 2 Staphylococcus intermedius 0.25 0.5 0.03 0.5 Enterococcus faecalis 0 2.0 2.0.0 2.0 Escherichia coli 0 0.03 0.03 0.05 0.03 Bacillus spp. 0 0.25 0.25 0.25 0.25 * The correlation between in vitro susceptibility data (MIC) and clinical response has not been determined. IDICATIOS AD USAGE: Zeniquin (marbofloxacin) tablets are indicated for the treatment of infections in dogs and cats associated with bacteria susceptible to marbofloxacin. COTRAIDICATIOS: Marbofloxacin and other quinolones have been shown to cause arthropathy in immature animals of most species tested, the dog being particularly sensitive to this side effect. Marbofloxacin is contraindicated in immature dogs during the rapid growth phase (small and medium breeds up to 8 months of age, large breeds up to 2 months of age and giant breeds up to 8 months of age). Marbofloxacin is contraindicated in cats under 2 months of age. Marbofloxacin is contraindicated in dogs and cats known to be hypersensitive to quinolones. WARIG: For use in animals only. Keep out of reach of children. Avoid contact with eyes. In case of contact, immediately flush eyes with copious amounts of water for 5 minutes. In case of dermal contact, wash skin with soap and water. Consult a physician if irritation persists following ocular or dermal exposure. Individuals with a history of hypersensitivity to fluoroquinolones should avoid this product. In humans, there is a risk of user photosensitization within a few hours after excessive exposure to quinolones. If excessive accidental exposure occurs, avoid direct sunlight. PRECAUTIOS: Quinolones should be used with caution in animals with known or suspected central nervous system (CS) disorders. In such animals, quinolones have, in rare instances, been associated with CS stimulation which may lead to convulsive seizures. Quinolones have been shown to produce erosions of cartilage of weight-bearing joints and other signs of arthropathy in immature animals of various species. The use of fluoroquinolones in cats has been reported to adversely affect the retina. Such products should be used with caution in cats. The safety of marbofloxacin in animals used for breeding purposes, pregnant, or lactating has not been demonstrated. ADVERSE REACTIOS: The following clinical signs were reported during the course of clinical field studies in dogs receiving marbofloxacin at dosages up to 2.5 mg/lb daily: decreased or loss of appetite (5.4%), decreased activity (4.4%), and vomiting (2.9%). The following signs were reported in less than % of cases in dogs: increased thirst, soft stool/diarrhea, behavioral changes, shivering/shaking/ tremors, and ataxia. One dog which had a seizure the day before study enrollment experienced a seizure while on marbofloxacin therapy. The following clinical signs were reported during clinical field studies in cats receiving.25 mg/lb/day: diarrhea (2.%) and soft stool (.4%). Vomiting was reported in less than % of cases in cats. DOSAGE AD ADMIISTRATIO: The recommended dosage for oral administration to dogs and cats is.25 mg marbofloxacin per lb of body weight once daily, but the dosage may be safely increased to 2.5 mg/lb. For the treatment of skin and soft tissue infections, Zeniquin tablets should be given for 2 3 days beyond the cessation of clinical signs for a maximum of 30 days. For the treatment of urinary tract infections, Zeniquin tablets should be administered for at least 0 days. If no improvement is noted within 5 days, the diagnosis should be re-evaluated and a different course of therapy considered. Drug Interactions: Compounds (e.g., sucralfate, antacids, and mineral supplements) containing divalent and trivalent cations (e.g., iron, aluminum, calcium, magnesium, and zinc) can interfere with the absorption of quinolones which may result in a decrease in product bioavailability. Therefore, the concomitant oral administration of quinolones with foods, supplements, or other preparations containing these compounds should be avoided. EFFECTIVEESS COFIRMATIO: Clinical effectiveness was confirmed in bacterial skin and soft tissue infections in dogs and cats and urinary tract infections (cystitis) in dogs associated with bacteria susceptible to marbofloxacin. Bacterial pathogens isolated in clinical field studies are provided in the Microbiology section. TARGET AIMAL SAFETY: : The toxicity of marbofloxacin was assessed in 2- to 4-month-old beagle Vomiting, reddened skin (usually involving the ears) and reddened mucous membranes were occasionally observed in all groups, including controls, but were noted most frequently in the 2.5 mg/lb group. Decreased food consumption and weight loss were significant in the 7.5 mg/lb and 2.5 mg/lb groups. o clinical lameness was noted in any of the treated animals. Minimal to slight lesions in the articular cartilage were observed in /8 placebo-treated animals and in 3/8 animals given 2.5 mg marbofloxacin/lb. Macroscopically, these lesions were vesicles, raised areas, or depressed, light-colored areas. Microscopically, these lesions were characterized by the presence of one or more of the following: fissuring, erosion, chondrocyte proliferation, fibrillation, or vertical splitting of the articular cartilage. These cartilage lesions in treated dogs were similar to those in control dogs, and were not typical of those produced by fluoroquinolones. In addition to the above pathologic alterations, red areas of articular cartilage were noted macroscopically in 0/8 placebo-treated dogs and in 2/8 dogs from each of the three marbofloxacin-treated groups. These areas usually correlated microscopically with areas of vascularity of the articular surface, but could not be confirmed microscopically in all animals. They consisted of large blood vessels in mature fibrous connective tissue, with no indication of active vascularization due to drug-induced damage. They were considered most likely to be developmental anomalies or normal variations of the joint surface and were not considered to be related to drug treatment. Marbofloxacin was administered to 2- to 4-month-old beagle dogs at a dosage of 25 mg/lb/day for 2 days. Decreased food consumption, vomiting, dehydration, excessive salivation, tremors, reddened skin, facial swelling, decreased activity and weight loss were seen in treated dogs. o clinical lameness was noted. As in the 42 day study, grossly visible, focal, red areas of articular cartilage were seen. These findings were noted in 2/6 placebo-treated dogs and in 4/6 marbofloxacintreated dogs. The foci were areas of fibrocartilage with prominent vascularization or increased vascularization of subchondral bone. Due to the appearance microscopically and macroscopically, these red foci were described as likely to be developmental anomalies or normal variations in articular cartilage. Marbofloxacin administered to 3- to 4-month-old, large breed, purpose-bred mongrel dogs at a dosage of 5 mg/lb/day for 4 days resulted in marked lameness in all dogs due to articular cartilage lesions. Lameness was accompanied by decreased appetite and activity. : Marbofloxacin was administered for 42 consecutive days to 24 cats approximately 8 months old (8 cats per treatment group) at the dosages of 2.5, 7.5 and 2.5 mg/lb/day (5.5, 6.5 and 27.5 mg/kg/day). Treatment with marbofloxacin did not produce adverse effects on body weights, food consumption, serum chemistry, urinalysis or organ weight parameters. Decreased segmented neutrophil counts were observed in some cats in all treatment groups, including the placebo group, but mean counts were significantly lower in the marbofloxacin-treated groups. In some cats, absolute neutrophil counts were below normal reference values (as low as 65 neutrophils/µl in a marbofloxacin-treated cat and as low as 882 neutrophils/µl in a placebo-treated cat). Other hematological observations were not adversely affected. Clinical signs were occasionally noted in cats in the highest dosage group: excessive salivation in 4/8 cats and redness of ear pinnae in 2/8 cats. Macroscopic changes in the articular cartilage of femurs were seen in one cat receiving 7.5 mg/lb and in 3 cats receiving 2.5 mg/lb. Microscopically, these gross lesions were related to a focal or multifocal chondropathy. Microscopic chondropathy not associated with macroscopic observations was also present in one cat treated with 2.5 mg/lb daily (X the upper end of the dose range) and one additional cat treated with 7.5 mg/lb daily. There was no evidence of lameness during the course of the study. A perivascular to diffuse dermatitis was seen microscopically in one mid-dose cat and 4 high-dose cats. Fundu scopic exam by a board-certified ophthalmologist and histologic examination of retina and optic nerve by ocular pathologists revealed no lesions in any of the treatment groups. Marbofloxacin was also administered orally to 6 cats approximately 8 months of age for 4 consecutive days at a dosage of 25 mg/lb/day (55 mg/kg/day). Clinical signs associated with drug intolerance were excessive salivation in 5/6 cats and redness of ear pinnae in all cats after 8 days of treatment. Emesis was noted occasionally in several cats and diminished activity was noted in one cat. Decreased food intake was noted in some animals, primarily males, when compared to controls. Perivascular to diffuse dermatitis was seen microscopically in the pinnae of all treated animals and in the standard skin samples of several animals. There was focal or multifocal articular chondropathy in 2/6 treated animals. One treated cat had a duodenal mucosal erosion and one treated cat had a pyloric ulcer. There were no observations of lameness and no adverse effects on hematology, clinical chemistry, urinalysis, or organ weight parameters. Fundu scopic examination by a board-certified ophthalmologist and histologic examination of retina and optic nerve by ocular pathologists revealed no lesions. A study was conducted to investigate the effect of marbofloxacin on articular cartilage of skeletally mature cats 2 4 months of age. Forty cats were randomly assigned to 4 groups of 0 cats each. Groups received placebo or marbofloxacin at dosages of.25, 3.75 or 7.5 mg/lb/day (2.75, 8.25 or 6.5 mg/kg/day) for 42 consecutive days. There were no treatment-related pathological changes in the joints or other tissues. Emesis and soft stools was noted in all treatment groups, including placebo, and increased in frequency with increasing dose and duration of treatment. Emesis was more apparent in the high-dose males. STORAGE CODITIOS: Store below 30 C (86 F). HOW SUPPLIED: Zeniquin tablets are available in the following strengths of marbofloxacin and bottle sizes: 25 mg scored tablets supplied in bottles that contain 00 or 250 tablets 50 mg scored tablets supplied in bottles that contain 00 or 250 tablets 00 mg scored tablets supplied in a 50 tablet bottle 200 mg scored tablets supplied in a 50 tablet bottle REFERECES:. Schneider M, et al: Pharmacokinetics of marbofloxacin in dogs after oral and parenteral administration. J Vet Pharmacol Therap 9:56 6, 996. To report suspected adverse effects, and/or obtain a copy of the MSDS, call -888-963-847. ADA #4-5, Approved by FDA Distributed by: Zoetis Inc. dogs administered marbofloxacin at 2.5, 7.5 and 2.5 mg/lb/day for 42 days. Kalamazoo, MI 49007 390600 390600 A&P Revised: Revised: January January 203 203